CHICAGO, IL -- February 22, 2000 -- Estrogen replacement therapy does not appear
to alter the mental deterioration associated with Alzheimer disease (AD),
according to an article in the February 23 issue of The Journal of the
American Medical Association (JAMA).

Ruth A. Mulnard, R.N., D.N.Sc., from the University of California, Irvine,
and colleagues enrolled women at sites that participated in the Alzheimer's
Disease Cooperative Study (ADCS) to assess whether estrogen replacement therapy
is associated with improving or stabilizing the deterioration of mental
functioning related to AD. The women enrolled in the study were diagnosed with
mild to moderate AD. They were randomly assigned to receive for a 12-month
period either 0.625 milligrams of estrogen per day (categorized as a "low
dose" for this study), 1.25 milligrams of estrogen per day (categorized as
a "high dose"), or a placebo pill. Of the 120 eligible women, 97
completed the trial. Women enrolled had to have had a prior hysterectomy, so
that they did not need to receive progesterone as well, a hormone necessary to
reduce the risk of endometrial cancer associated with taking estrogen alone.

"Estrogen replacement therapy for one year did not slow disease
progression nor did it improve global, cognitive or functional outcomes in women
with mild to moderate AD," the authors write. "The study does not
support the role of estrogen for the treatment of this disease. The potential
role of estrogen in the prevention of AD, however, requires further research."

According to background information cited in the study, several reports from
small clinical trials have suggested that estrogen replacement therapy may be
useful for the treatment of AD in women, but this study was conducted for a
longer period and enrolled more women than past studies.

The researchers used a semi-structured interview based on the ADCS's version
of the Clinical Global Impression of Change (CGIC) scale to assess the changes
in the mental functioning of the participants. On the 7-point CGIC scale, the
average score for those participants receiving estrogen was 5.1 and the average
score for those receiving placebo was 5.0. Of the participants receiving
estrogen, 80 percent worsened compared with 74 percent of those receiving
placebo.

The researchers also found no significant difference between those women who
received estrogen therapy and those who received a placebo in scores that
measured mood, memory, attention, language skills, motor function and activities
of daily living. The only scale that showed a significant difference between the
estrogen and placebo groups was the Clinical Dementia Rating Scale, which
associated receiving estrogen with worsening performance.

The researchers found improvement in Mini-Mental State Examination scores
after brief exposure (at the 2-month follow-up) to the lower dose of estrogen,
but this improvement did not persist when measured at subsequent follow-ups.

Citing previous research the authors note: "Alzheimer disease affects
more than 4 million Americans and is one of the most frequent obstacles to
healthy aging in this country. Women appear to be at higher risk for developing
AD, only in part due to increased longevity. Because women with AD also live
longer than men with AD, there are approximately twice as many women as men in
the population with this disorder. It has been suggested that the abrupt decline
of estrogen production in postmenopausal women may be associated with a
vulnerability of women to develop AD." (JAMA. 2000;283:1007-1015)